The Genes Responsible for Immune System Reset after Infection
We’ve all been sick before, the aches and pains that come with it– most of the time including a fever — are all responses to our immune system kicking into high gear. But what if your body didn’t reverse course and go back to a, let’s call it” relaxed state.” Once the battle is won, the body’s efforts would be wasted on energy costing defense. A bad thing when the body really should be focusing on repairing the damage done by the foreign invaders.
How this transition, from attack to repair happened was not quite understood. Until now that is, researchers have uncovered the genes that are normally activated during recovery from bacterial infection. The finding could lead to ways to jumpstart this recovery process and possibly fend off autoimmune diseases and chronic inflammatory disorders — such disorders are thought to result from the body staying in attack mode for too long.
“While the steps involved in recognizing microbial pathogens and inducing the immune response have been extensively studied, the pathways involved in host recovery after an infection are not well understood,” said Alejandro Aballay, Ph.D.
To examine the biological changes associated with this transition from wartime to peacetime the team infected the worm C. elegans with the common bacterial pathogen Salmonella enterica.
The researchers used gene chip technology to identify genes in the worm that were “turned off” or “turned on” during that initial infection. Then they treated the worm with the antibiotic tetracycline and looked to see what genes were dampened or activated as the organism recovered from infection.
They discovered that as the infection resolves, genes involved with stimulating the immune response were turned off, while genes involved in returning to business as usual—a process known as “cellular homeostasis” – were turned on. These recovery genes play important roles in repairing tissue damage, eliminating bacterial toxins and clearing the cellular fighters that could cause excessive inflammation and further harm tissues.
When the researchers looked closer at the genes involved in recovery, they discovered many were controlled by the ELT-2 transcription factor, a type of master switch that had already been shown to regulate when and where immune response genes were expressed. The group showed that shutting down this master switch prevented infected animals from recovering with antibiotic treatment, showing that ELT-2 functions not only in defense but also in recovery.
“Our studies indicate that host or bacterial signals during the initial decline in infection may shift ELT-2’s duties from priming the innate immune to protecting against chemical insults,” Aballay said. “This opens a number of possibilities for further research.”
A number of studies in C. elegans have shown that the worm’s nervous system, which can respond rapidly to all sorts of environmental stimuli, is ultimately responsible for activating the immune system in response to bacterial infection. So now the team plans to conduct experiments in the worm to determine whether the nervous system also controls the recovery after infections have been cleared.
Research done on C. elegans might not sound like it should apply to us humans, but as I’ve mentioned in the past, it is still a very good indicator of where to go next. With new information (and more to come) we will hopefully be able to unlock the secrets of our immune system and with it, hope for anyone who suffers from autoimmunity.
Brian Head,, & Alejandro Aballay (2014). Recovery from an Acute Infection in C. elegans Requires the GATA Transcription Factor ELT-2 PLoS Genetics : 10.1371/journal.pgen.1004609